title: Specific gut commensal flora locally alters T cell tuning to endogenous ligands.
abstract: Differences in gut commensal flora can dramatically influence autoimmune responses, but the mechanisms behind this are still unclear. We report, in a Th1-cell-driven murine model of autoimmune arthritis, that specific gut commensals, such as segmented filamentous bacteria, have the ability to modulate the activation threshold of self-reactive T cells. In the local microenvironment of gut-associated lymphoid tissues, inflammatory cytokines elicited by the commensal flora dynamically enhanced the antigen responsiveness of T cells that were otherwise tuned down to a systemic self-antigen. Together with subtle differences in early lineage differentiation, this ultimately led to an enhanced recruitment of pathogenic Th1 cells and the development of a more severe form of autoimmune arthritis. These findings define a key role for the gut commensal flora in sustaining ongoing autoimmune responses through the local fine tuning of T-cell-receptor-proximal activation events in autoreactive T cells.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. pascal.chappert@inserm.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Chappert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000382:microbiology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000382:microbiology; D017252:CD3 Complex / Q000235:genetics; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D003013:Clostridium / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D001324:Autoantigens; D017252:CD3 Complex; C485468:Cd3e protein, mouse